The circulatory responses to lowered levels of oxygen (O2) tension in arterial blood include a preferential diversion of blood flow away from splanchnic areas and skeletal muscle to protect the heart and brain by increasing their perfusion. This implies that the greater portion of any O2 deficit incurred during severe hypoxia is borne by muscle and gut. This project will ascertain how much of muscle O2 uptake is mandatory during hypoxia and whether there must be repayment of any O2 deficit by increased O2 uptake during a normoxic recovery period. Preliminary studies have shown that combined alpha- and beta-adrenergic blockade prevented the usual post-hypoxic hyperemia in canine hindlimb. Because changes in O2 uptake are usually accompanied by changes in blood flow, adrenergic receptors may have altered O2 supply or energy demand by muscle during hypoxia. The role of adrenergic receptors will be investigated, therefore, by the use of specific blockers and agonists. The experiments will be done on anesthetized, paralyzed dogs ventilated with air or low O2 mixtures. The left hindlimb, less the paw, will have its venous outflow isolated so that blood flow and O2 uptake can be measured. Hindlimb and whole body O2 uptakes will be measured continuously so that, by relating them to control values, total and regional O2 deficits during hypoxia and excess O2 uptake during recovery can be calculated and compared. The separate and combined effects of denervation, alpha- and beta-adrenergic blockade upon the relationship between O2 deficit and its repayment will be examined in the hindlimb and the whole body. Specific alpha- and beta-agonists will be used during hypoxia to see the maximum effects that might have been exerted by catecholamine release at sympathetic endings or into circulating blood from the adrenals. The results may show that skeletal muscle does not obligate a large portion of whole body O2 debt repayment following hypoxia in spite of incurring most of the O2 deficit. That would imply that a portion of resting skeletal muscle O2 uptake is devoted to heat generation rather than to its own cellular function.